CoMFA and molecular docking studies of benzoxazoles and benzothiazoles as CYP450 1A1 inhibitors

For better understanding of the molecular interactions of inhibitors with CYP450 1A1, a series of benzoxazoles and benzothiazoles were analyzed by comparative molecular field analysis (CoMFA) and molecular docking. Two conformer-based alignment strategies were employed to construct reliable CoMFA models. The best CoMFA model yielded a predictive correlation coefficient r2pred value of 0.809. Furthermore, a three-dimensional model of CYP450 1A1 was generated by homology modeling using CYP450 1A2 as a template, and docking of 48 CYP450 1A1 inhibitors into the putative binding sites of the CYP450 1A1 were studied. The results obtained from this study will be helpful in the design of potentially active CYP450 1A1 inhibitors.

Graphical abstractA three-dimensional model of CYP450 1A1 was generated by homology modeling using CYP450 1A2 as a template, and CYP450 1A1 inhibitors of benzoxazoles and benzothiazoles were docked into the putative binding site of the CYP450 1A1. The results give a deep insight into the hydrogen-bonding interactions between the inhibitors and residues in the active site of CYP450 1A1.Figure optionsDownload full-size imageDownload as PowerPoint slide